Chromatin biology laboratory
Among the greatest challenges facing organisms is how to detect and efficiently respond to life-threatening environmental changes (including nutrient deprivation) which are intimately associated to metabolic fluctuations and certain forms of stress (e.g. oxidative or genotoxic). The response to these stress conditions has a major impact in the maintenance of genome integrity and is intimately linked to the onset of many human pathologies, including cancer, endocrine disorders and cardiovascular and neurodegenerative diseases. The onset and development of haematological pathologies like leukemia are strongly influenced by this response and therefore it may be a relevant treatment approach. Our main goal is to define the epigenetic mechanisms that rule this response and its functional implications in genome stability and cancer through a multidisciplinary approach that combines Biochemistry, Genetics, Molecular and Cell Biology. In particular, we focus our studies on the sirtuin family of proteins, which coordinate the response to these forms of stress.
The Chromatin Biology Laboratory is recognized for its experience in the study of response mechanisms under stress conditions. In particular, the group's main objective is to define the role of the sirtuin family of enzymes in the regulation of genome stability and epigenetics in response to stress and their impact in cancer and aging. Although the majority of sirtuins are NAD+-dependent deacetylases, some family members also harbour a second enzymatic activity, an ADP-ribosyltransferase (ADPRT) activity. This functional duality is intriguing and is one focus of the group’s work. Sirtuins play an important role in the hematopoietic system; as they have been seen to be involved in the maintenance of hematopoietic stem cells, cell differentiation and immune response, also they are associated with the development of some types of leukemia. Since it was set up, the laboratory has described various mechanisms involved in genome stability protection and stress response (Mol Cell 2011, Genes & Dev 2013, EMBOJ 2016, Epigenetics 2017, Cel. Rep. 2017, Nat comm. 2018). The group has participated in collaborations on other epigenetic aspects associated with the control of genomic stability (Dev. Cell 2013, NAR 2017, J of Hepatology 2017, Sci Rep 2017) and has participated in the main discussions in the field of sirtuins and the stress response (Genes & Dev 2009, Science 2010, Cancer Cell 2012, Oncogene 2014, FEBS J 2015, Proteomics 2017). In its mission to understand the contribution of sirtuins to stress response and the protection of genome stability, the work of the group covers a range of research from basic aspects of sirtuin biology to the study of their contribution to the development of human pathologies, such as leukemia and aging. In this sense, the major lines of work of the group are:
1. Understanding the enzymatic duality of sirtuins and their specific contribution to sirtuin function. In particular, we focus our efforts in the poorly understood ADPRT activity.
2. Sirtuin-dependent mechanisms of genomic stability including constitutive heterochromatin integrity, DNA damage signalling and repair, as well as cell cycle checkpoint control.
3. The role of sirtuins in B-cell differentiation.
4. Functional implication of sirtuins in cancer, and in particular in the context of hematopoietic pathologies like leukemia and lymphoma.
5. Development of new methodology to measure in vivo sirtuins activity.
Sandra Ibarra Award. Fundación Sandra Ibarra. Madrid, Spain
Chromatin Biology Lab recognized as “Emerging Group”. Catalonian Government. AGAUR, Generalitat de Catalunya
2014 and 2017
Chromatin Biology Lab recognized as “Consolidated Group”. Catalonian Government. AGAUR, Generalitat de Catalunya
Industrial Doctorate Program. Mesostetic-Pharma/UB/IDIBELL. Generalitat de Catalunya
|Alex Vaquero||Group Leaderfirstname.lastname@example.org|
|Anna Marazuela||Research Associateemail@example.com|
|Berta Vázquez||Postdoctoral Investigatorfirstname.lastname@example.org|
|Irene Fernández||Postdoctoral Investigatoremail@example.com|
|María Espinosa||Postdoctoral Investigatorfirstname.lastname@example.org|
|Jéssica González||PhD Studentemail@example.com|
|Josema Castelló||PhD Studentfirstname.lastname@example.org|
|Andrés Gámez||PhD Studentemail@example.com|
SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear laminaNucleic Acids Res. 47(15):7870-7885 (2019). , .
SIRT1/2 orchestrate acquisition of DNA methylation and loss of histone H3 activating marks to prevent premature activation of inflammatory genes in macrophageNucleic Acids Research 48, 665–681 , .
Sirtuin 1 Inhibiting Thiocyanates (S1th)-A New Class of Isotype Selective Inhibitors of NADFront Oncol 2020, 10 657. Epub 30 Apr 2020
SirT7 auto-ADPribosylation regulates glucose starvation response through macroH2A1Sci.Adv. 6(30): eaaz2590 , .
|Project leader:||Alex Vaquero|